flavopiridol and irinotecan in treating patients with advanced solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. combining more than one drug may kill more tumor cells. purpose: phase i trial to study the effectiveness of combining flavopiridol with irinotecan in treating patients who have locally advanced or metastatic solid tumors.

objectives: * determine the maximum tolerated dose of flavopiridol when combined with irinotecan in patients with advanced solid tumors. * determine the clinical pharmacokinetics of this regimen, as well as the plasma levels of the active metabolite sn-38 and metabolic product sn-38 glucuronide in these patients. * determine, in a preliminary manner, the therapeutic activity of this regimen in these patients. * determine the role of p21 relative to treatment response and apoptosis in these patients treated with this regimen. outline: this is a dose-escalation, open-label, non-randomized study of flavopiridol. patients receive irinotecan iv over 30 minutes followed 7 hours later by flavopiridol iv over 1 hour on days 1, 8, 15, and 22. treatment continues every 6 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity. during the first week of the second course, patients receive flavopiridol alone on day 1 and irinotecan alone on day 2. cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 or more of 6 patients in the initial cohort experience dose limiting toxicity during the first course of treatment. an additional 10 patients are treated at the mtd. projected accrual: a total of 44-50 patients will be accrued for this study within 1 year.

Eligibility criteria:
disease characteristics: * histologically proven locally advanced or metastatic solid tumor that is refractory to standard therapy or for which no standard therapy exists * eligible for treatment at the maximum tolerated dose only if disease accessible for tissue biopsy by tru-cut, ct guidance, or endoscopy * pleural effusions or abdominal ascites do not constitute adequate tissue for biopsy * no known cns metastasis or primary cns tumor patient characteristics: age: * 18 and over performance status: * karnofsky 60-100% life expectancy: * not specified hematopoietic: * wbc at least 3,500/mm\^3 * total neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin no greater than 1.5 mg/dl * sgot and sgpt no greater than 2.5 times upper limit of normal renal: * creatinine no greater than 1.5 mg/dl cardiovascular: * no cardiac arrhythmias, congestive heart failure, or myocardial infarction within the past 6 months other: * not pregnant or nursing (during and for at least 2 months after study) * negative pregnancy test * fertile patients must use effective contraception during and for at least 2 months after study * no concurrent serious or uncontrolled infection * hiv negative * no other medical condition that would preclude study participation prior concurrent therapy: biologic therapy: * at least 4 weeks since prior immunotherapy and recovered chemotherapy: * at least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered * prior irinotecan allowed endocrine therapy: * not specified radiotherapy: * at least 4 weeks since prior radiotherapy and recovered surgery: * see disease characteristics other: * recovered from prior therapy * no other concurrent investigational medication * no concurrent vitamins (except a single multivitamin tablet), antioxidants, or herbal preparations or supplements * no concurrent subcutaneous heparin or heparinoids

Keywords: unspecified adult solid tumor, protocol specific